Progress Reports

Reporting Period:

Year 2

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<p>This award was meant to test efficacy of candidate drugs for calcific aortic valve disease (CAVD) in an animal model and in a broader range of patient cells. CAVD is the third most common form of heart disease and despite the over 100,000 valve replacements performed for this disease in the US each year, there is no medical treatment currently. The candidate drugs tested here were discovered using human pluripotent stem cells derived from patients with the disease. We identified one specific drug compound that was very effective in not only restoring the abnormalities typical of the disease process in human cells in a dish, but also was very effective in preventing aortic valve calcification in mice, including preventing aortic valve thickening and narrowing, which is ultimately what requires replacement in patients. This drug will now be developed further as a potential novel therapy for CAVD.</p>

Determine efficacy of nine drugs validated in N1+/– iPSC-ECs in preventing CAVD in a mouse model.

Initiate studies of optimal dosing and timing of potential therapeutic compound, which will be determined by best efficacy in Activity 5.

Statement of Benefit to California:

This research will benefit California by developing drugs to treat Calcific Aortic Valve Disease (CAVD), a major unmet medical need that imposes a serious economic burden. The only clinical option is valve replacement, with 100,000 patients receiving transplants per year in the US. To address this, we will use a stem cell-based platform based on CAVD patient-derived stem cells to test drugs, already proven to be safe, that normalize gene dysregulation and prevent CAVD.